Human melanoma invasion and subsequent metastasis are more realistically studied by inoculating melanoma cells in locations and environments which mimic the in vivo situation. Human cutaneous melanomas usually have an initial horizontal growth phase followed by a vertical invasive phase. To study this early process of invasion, orthotopic in vivo models for melanoma invasion which mimic this pattern must be developed. This will be accomplished by injection of human melanoma cells into subepidermal blisters on athymic nude mice and surgical implantation of melanoma cells with artificial extracellular matrices onto nude mice. Melanoma dermal invasion will also be studied in vitro in order to provide invasion models that are more easily manipulated than in vivo models, and also to conserve the numbers of animals required for invasion studies. The membrane invasion culture system (MICS) will be used to either quantitate variations in the invasion of different types of dermal collagen (types I and III collagen vs. type IV collagen) by melanoma cell lines or to selectively enhance melanoma cell lines for their abilities to invade these types of collagen for further in vitro and in vivo invasion studies. Invasion of type I or type IV specific thick collagen gels by melanoma cells in silicone invasion chambers in vitro will allow study of invasion of specific types of collagen found in the dermis of histology and (in the future) in situ hybridization. A normal human skin acellular dermis model will be prepared to study melanoma invasion of normal human dermis with an intact basement membrane zone in vitro. Correlating the invasion observed in the in vitro and in vivo models and extending the study to metastasis development will allow the study of factors which enhance or decrease invasion. It is proposed that further studies of the factors that affect invasion may lead to new therapies for melanoma.